Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA.

Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo.

PURPOSE Ribonucleotide reductase (RR) is a therapeutic target for DNA replication-dependent diseases such as cancer. Here, a potent small interfering RNA (siRNA) duplex against the M2 subunit of RR (RRM2) is developed and shown to reduce the growth potential of cancer cells both in vitro and in vivo. EXPERIMENTAL DESIGN Three anti-RRM2 siRNAs were identified via computational methods, and the...

Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction restores sensitivity to hydroxyurea cytotoxicity.

BACKGROUND Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint, a part of the S-phase checkpoint that responds to DNA damage by inhibiting late origin firing. It also transactivates RR and other genes involved in DNA replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb-assoc...

Potent subunit-specific effects on cell growth and drug sensitivity from optimised siRNA-mediated silencing of ribonucleotide reductase

Ribonucleotide reductase (RR) has an essential role in DNA synthesis and repair and is a therapeutic target in a number of different cancers. Previous studies have shown that RNAi-mediated knockdown of either the RRM1 or RRM2 subunit sensitizes cells to the cytotoxic effects of the nucleoside analogs and more recently it has been shown that RRM2 knockdown itself has a growth inhibitory effect. ...

An analysis of human equilibrative nucleoside transporter-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and excision repair cross-complementing gene-1 expression in patients with resected pancreas adenocarcinoma: Implications for adjuvant treatment

Herpes simplex virus ribonucleotide reductase induced in infected BHK-21/C13 cells: biochemical evidence for the existence of two non-identical subunits, H1 and H2.

In nearly all systems studied, ribonucleotide reductase consists of two non-identical subunits. We present here the results of our study on herpes simplex virus (HSV) ribonucleotide reductase in favour of the existence of two subunits, H1 and H2, different from the mammalian subunits, M1 and M2. First, although the viral subunits could not be separated by Blue Sepharose chromatography (unlike m...